RESEARCH Open Access

A multimodal intervention program tocontrol a long-term Acinetobacterbaumannii endemic in a tertiary carehospitalR. Valencia-Martín1, V. Gonzalez-Galan1, R. Alvarez-Marín1* , A. M. Cazalla-Foncueva1, T. Aldabó2, M. V. Gil-Navarro3,I. Alonso-Araujo2, C. Martin2, R. Gordon4, E. J. García-Nuñez5, R. Perez5, G. Peñalva1, J. Aznar1, M. Conde1,J. M. Cisneros1 and In representation of A. baumannii eradication program

Abstract

Background: Acinetobacter baumannii causes frequently nosocomial infections worldwide. Its ability to survive ondry surfaces facilitates its spread and the persistence of endemic situations, especially in the intensive care units(ICUs).The objective of this paper is to describe a multicomponent intervention program designed to control ahyperendemic persistence of multidrug-resistant A. baumannii (MDR-Ab) and to characterize its impact.

Methods: Design: Quasi-experimental intervention study based on open cohorts.Setting: Public tertiary referral centre. Period: January 2009–August 2017.Intervention: multifaceted program based on environmental decontamination, hand hygiene, antimicrobialstewardship, contact precautions, active surveillance, weekly reports and regular meetings.Analysis: joinpoint regression and interrupted time-series analysis.

Results: The intervention was successfully implemented. Through the study period, the compliance with contactprecautions changed from 0 to 100% and with hand hygiene, from 41.8 to 82.3%. Between 2012 and 2016, theantibiotic consumption decreased from 165.35 in to 150.44 daily-defined doses/1000 patients-days in the ICU. Theincidence density of MDR-Ab in the ICU was 10.9 cases/1000 patients-days at the beginning of the intervention.After this moment, the evolution of the incidence density of MDR-Ab was: between months 0 and 6°, it remainedstable; between months 7° and 10°: there was an intense decrease, with an average monthly percentage change(AMPC) = − 30.05%; from 11° month until the end, the decrease was lighter but continuous (AMPC:-2.77%),achieving an incidence density of 0 cases/1000 patients-days on the 18° month, without any new case for 12months. From the 30° month until the end of the study period, several little outbreaks of MDR-Ab were detected,all of them rapidly controlled. The strains of MDR-Ab isolated during these outbreaks were not clonally related withthe previously endemic one, which supports its eradication from the environmental reservoirs.

Conclusion: The multicomponent intervention performed by a multidisciplinary team was effective to eradicate theendemic MDR-Ab.

Keywords: Acinetobacter baumannii, Infection control, Outbreak, Endemic

© The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, andreproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link tothe Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

* Correspondence: rocioalma@gmail.com1Departments of Infectious Diseases, Microbiology, and Preventive Medicine,University Hospital Virgen del Rocío–Institute of Biomedicine of Seville,Avenida Manuel Siurot s/n, 41013 Seville, SpainFull list of author information is available at the end of the article

Valencia-Martín et al. Antimicrobial Resistance and Infection Control (2019) 8:199 https://doi.org/10.1186/s13756-019-0658-4

BackgroundAcinetobacter baumannii is a frequent etiology ofnosocomial infections worldwide, posing a major challengedue to its great ability to develop resistance against antibi-otics [1, 2]. In recent years, most reported clinical isolatesare multidrug-resistant, and several outbreaks caused byextremely-drug resistant (XDR) or even pan-drug resistant(PDR) have been described [3–5]. Hospital outbreaks andendemic situations are expedited by the capacity of A. bau-mannii to survive on all kind of surfaces [6]. However, al-though some outbreaks could be controlled by eliminatingan environmental reservoir [7], in many centres all over theworld affected by endemic situations with occasional super-imposed outbreaks [8–11], endemicity tipically persists aftercontrolling the outbreaks flaring up. This problem affectsespecially to Intensive Care Units (ICUs) [2, 12].Our hospital experienced a two decades-long hyperen-

demic situation with A. baumannii and even an out-break of PDR-A. baumannii in 2002 [5]. Since 2008,most clinical isolates were carbapenem-resistant, all ofthem susceptible to colistin. Despite several interven-tions, including hand hygiene, contact precautions andan antimicrobial stewardship program, the incidence ofmultidrug resistant A. baumannii (MDR-Ab) did not de-crease. In late 2012, a second outbreak of XDR-A. bau-mannii-resistant to colistin was declared in the adultsICU.After the epidemiological investigation and environmen-

tal and surveillance cultures, a molecular characterizationof the XDR isolates by pulsed-field gel electrophoresis(PFGE) [13] confirmed that they were closely related, ac-cording to the Tenover criteria [14]. With the purpose offacing this situation, we designed an alternative interven-tional program to control the outbreak and the endemicsituation. On this paper, we report the multicomponentprogram developed and its impact on the incidence ofMDR-Ab.

MethodsSettingUniversity Hospital Virgen del Rocío (Seville, Spain) is a1367 bed-centre with two adult ICUs, which have sixmultibed open wards for medical and surgical patients(50 beds), and two wards for trauma and neurosciencesareas divided into rooms for one patient each (18 beds).This is a reference centre for severe trauma, neurosur-gery, burn patients and solid organ and bone marrowtransplantations. During the studied period, the hospitaland ICUs had, respectively, an average of 52,593 and3379 inpatient episodes per year.

Study designThis is a quasi-experimental intervention study, based onopen cohorts of all the patients admitted to the hospital

from the 1st January 2009 to the 31stAugust 2017, havinga pre-intervention period of 46months and a post-intervention period of 58months.

Infection control teamA multidisciplinary team, composed of an infection con-trol and hospital hygiene specialist, a microbiologist, apharmaceutical specialist, an infectious diseases phys-ician and three nurses with expertise in infection con-trol, designed and led the intervention program.

Intervention programA multifaceted program was implemented. All the mea-sures agreed the current recommendations of theCenters for Disease Control and Prevention (CDC) [15].

Environmental decontaminationAn exhaustive environmental cleaning policy was insti-tuted. The disinfectant used were a hypochlorite-baseddisinfectants; for the handling of not-disposable medicalproducts in which this disinfectant was not appropriate,a wipe disinfectant containing benzalkonium chlorideand propane-1,2-diol was used. Medical products wereexclusive of each colonized of infected patient. Dispos-able medical products were discarded once the patientdid not need them any more following the CDC recom-mendations [16], and not-disposable products werecleaned following the procedures previously described.To verify the environmental decontamination proced-

ure, two specific checklists were created: one for thegeneral environmental cleaning and the other for med-ical equipment disinfection. These checklists had to befilled by the cleaning staff every time that any cleaningprocedure was performed, and at least twice each day;the percentage of compliance was monitored weekly.The infection control team met several times with thecleaning staff for educational purposes and feedback ofthe results.Every ICU ward was sequentially closed for a terminal

cleaning at the beginning of the program, and periodic-ally at least thrice a year. Afterwards, every bedside ofthe ICU and the rooms in other wards from which a col-onized patient was discharged underwent terminalcleaning as well.

Hand hygiene instruction and surveillanceHand hygiene education courses were provided to the ICUstaff the first weeks after the XDR-Ab outbreak, and period-ically afterwards, emphasizing on training on newly incor-porated staff. The hand hygiene training was based on theperformance of periodic workshops in which the five mo-ments for hand hygiene were remembered and the tech-nique was trained using an UV glow box. During the firstyear, structured observation of hand hygiene compliance

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during the daily care activity was performed weekly by thenurses of the infection control team in the ICU, followingthe recommendations and observation tool of the WHO[17]. Afterwards, this observation was performed periodic-ally (at least once each month). The percentage of compli-ance was included in the weekly reports.

Antimicrobial stewardship programUntil the outbreak of XDR-Ab was controlled, colistinwas restricted, needing pre-authorization and being re-vised the indication and duration of every colistincourse. Afterwards, the educational stewardship programpreviously set in the hospital [18] was enhanced in theICUs, adding a weekly feedback of the antibiotic con-sumption data to the staff.

Isolation and contact precautionsContact precautions, following the CDC recommenda-tions [16], were already mandatory for patients carryingMDR-Ab. In addition, we implemented the surveillanceof its compliance and displayed information posters inevery affected unit.Contact precautions were maintained through the

whole admission period for patients with MDR-Ab.

Active surveillance for MDR-Ab colonizationAll patients admitted to adult ICUs were screenedweekly. Surveillance cultures were obtained by rectaland pharyngeal swabs.

Weekly reportA weekly report was made with the evolution of the se-lected indicators. It includes the level of compliance ofthe measures and the results achieved. Definitions andindicators are described below.

Regular meetings with the staff of the affected areasThe infection control team met weekly with the staff ofthe ICUs (physicians, nurses, assistant nurses, hospitalattendants, housekeepers) to discuss the results of theweekly report, and to take additional measures when ne-cessary. Additionally, the medical and nurse directorswere informed by weekly email for the whole period.

Definitions and indicatorsA. baumannii was defined as MDR or XDR following thecriteria of Magiorakos et al. [19], which consider that A.baumannii is MDR when non-susceptible to ≥1 agent in≥3 antimicrobial categories (including aminoglycosides, car-bapenems, fluorquinolones, antipseudomonal penicillins+β-lactamases inhibitors, extended spectrum cephalosporins,trimethoprim-sulphamethoxazole, ampicillin-sulbactam,polymixins and tetracyclines) and XDR when non-susceptible to ≥1 agent in all but ≤2 of the same categories.

If the susceptibility to one antimicrobial was not tested, itwas classified as “resistant” (see below). The main outcomewas the incidence density of MDR-Ab in clinical samples,defined as the number of patients newly infected or colo-nized with MDR-Ab per 1000 patient-days. Surveillancesamples were excluded because of their absence in the pre-intervention period. An isolate of MDR-Ab was consideredas a new episode after 365 days of the last positive culturein the same patient or when the initial infection was curedand MDR-Ab was not isolated in three rectal swabs per-formed in three consecutive weeks. Hand hygiene compli-ance was expressed as the percentage of correct actionsover all the observed ones [20]. The appropriateness of theisolation and contact precautions was evaluated with a formdesigned for this purpose. The global compliance was thepercentage of patients with a correct response to all theitems over the total of patients under contact precautionsobserved. Environmental and medical equipment cleaningcompliance was evaluated by checklists designed for thispurpose, completed by the responsible staff (housekeepersand assistant nurses, respectively). They were stated as thepercentage of correct actions of each item over the total.Antimicrobial consumption was measured in Daily DefinedDoses (DDD) per 1000 patients-days. Hand hygiene, con-tact precautions and cleaning compliance were surveyedjust in the ICUs; all the others in the whole hospital, analys-ing separately the ICUs.

Microbiological proceduresActive surveillance for MDR-Ab colonization wasperformed in all patients admitted to the ICU withat least prior 48 h hospitalization [21]. The culturemedia used was Brilliance™ CRE Agar, a chromo-genic screening plate for the detection ofcarbapenem-resistant strains with high sensitivityand specificity and whose results are available in just18–24 h. Each isolate was identified by the Matrix-assisted laser desorption/ionization time of flightmass spectrometry (MALDI-TOF MS- Brucker®).Susceptibility testing to colistin and meropenem ofthe isolates was studied by E-test© (AB Biodisk,Sweden) according to the manufacturer’s recommen-dations. Susceptibility to other antibiotics was per-formed by using commercial microdilution methods(PMicroScan combo NC58. BeckamCoulter. USA).Amikacin, ampicillin/sulbactam, imipenem, minocy-cline and tigecycline were tested in all the isolates.Due to the generalized resistance to some groups ofantibiotics (fluorquinolones, antipseudomonal peni-cillins+β-lactamases inhibitors, extended spectrumcephalosporins, trimethoprim-sulphamethoxazole andtetracycline) among the isolates of A. baumanniifrom our hospital in previous years, the susceptibilityto them was tested just in a variable proportion of

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isolates. The breakpoints used were those recom-mended by EUCAST in each time frame [22].Molecular typing using PFEG was performed for the ini-

tial outbreak investigation, as mentioned above, and to thenew isolates of the outbreaks that occurred after the eradi-cation of the endemic. Plug preparation, lysis, cell wash-ing, restriction digestion (60 U of ApaI), andelectrophoresis were performed as previously described[13]. PFGE was performed by using a clamped homoge-neous electric field electrophoresis (CHEF) DRIII appar-atus (Bio-Rad Laboratories, Hercules, CA). The conditionsemployed were as follows: temperature of 14 °C, voltage of6 V/cm, run time of 19 h, and switch time of 5 to 20 s.The images obtained were processed with Bio- Rad Mo-lecular Imager® GelDoc™ XR+ with Lab™ Software. PFGEclustering was determined by using the unweighted-pairgroup method with arithmetic averages (UPGMA) and byusing Dice’s coefficient. The tolerance was set at 1%. Allcalculations were performed by using InfoQuest software(Applied Maths, Saint-Martens-Latem, Belgium). The re-sults of the PFGE typing were compared according to theTenover criteria [14].

Statistical analysisTo estimate changes in the observed trends we used ajoinpoint regression analysis [23], with previous evalu-ation of homocedasticity and existence of autocorrel-ation for each variable using SPSS Version 19.0(Armonk, NY: IBM Corp.). These models give a doubleresult: they identify the time point in which the trendchanges and they also estimate the observed trend ineach time interval. A maximum of three turning pointswere searched for each regression analysis. Statistical sig-nificance was set in an alpha error of 0.05. The softwareused was Joinpoint Regression Program, Version 4.5.0.1- June 2017 (Statistical Methodology and ApplicationsBranch, Surveillance Research Program, National CancerInstitute, Bethesda, MD, USA). In addition, we per-formed an interrupted time series (ITS) analysis with Rversion 3.4.3.

ResultsRates of MDR-Ab colonization and infectionThe outbreak of XDR-Ab affected five patients and wascontrolled in three weeks. The incidence density of MDR-Ab was 10.9 cases/1000 patients-days at the beginning ofthe enhanced infection control program. The monthlytracking of this incidence is represented in Fig. 1. Sixtyweeks after the multifaceted program started, the inci-dence achieved 0 cases/patients-days in the ICUs. No newcases were described for 34 weeks since week 94. Later,there have been several outbreaks after the eradication ofthe endemic situation, caused by patients previously colo-nized at the moment of the admission (Fig. 1). On Fig. 2,

PFGE shows the restriction profiles of genomes extractedfrom isolates causing outbreaks occurred in 2015 andcompares to those caused in 2009. The differences onbands that are observed among the lanes indicate that theisolates causing these outbreaks were distinct from thoseof the preceding years at level of their genomes, applyingTenover criteria [14].The incidence density of MDR-Ab bacteraemia at the

beginning of the program was 0.026 cases/1000 patients-days, with a crude mortality of 50%. Three trimesterslater, the incidence achieved 0.000 cases/1000 patients-days and no new cases of MDR-Ab bacteraemia havebeen observed.The joinpoint regression analysis of the MDR-Ab rates

is given in Table 1. This analysis selected the beginningof the multifaceted intervention as the point of trendchange, either in the wards or the ICU (Fig. 3). In theICU there was an upward baseline trend (AMPC:0.23%); 6 months after the intervention (month 52) weobserved a trend change followed by an intense decreaseduring four months (AMPC: − 30.05%), continuing witha significant tendency towards zero (AMPC: − 2.77%)until the end of the period. In the rest of adult wards theAMPC underwent a change prior to the implementationof the program in month 34 (1.07%), followed by a pro-longed decline (AMPC: − 4.02%) maintained for 18months, moving to a final trend not statistically signifi-cant (AMPC: 3,94%).For the interrupted time series analysis, we consid-

ered a 6-month lag to reach endemic control (timenecessary to decrease the incidence density rates of5‰). In the ICU we observed an increasing baselinetrend followed, after the phase-in period, by a de-creasing non-linear trend throughout the rest of theperiod (Fig. 4).

Environmental decontaminationThe first weeks, the overall environmental cleaningcompliance was 83%. After 14 weeks, a 100% of com-pliance in all the items of the checklists wasachieved.

Contact precautions and hand hygieneThe first evaluation revealed that the adherence to allthe indicated measures of contact precautions wascorrect in 0% of the cases. Although all the colo-nized/infected patients were visibly identified, the in-dividual protection equipment was correctly locatedjust in 5.6% of them and only 22.2% received the ap-propriate hygiene, while the visits policy was system-atically incorrect. Two years later, the compliancewith the contact precautions was 100% in all the eval-uated items.

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The compliance with the hand hygiene was 41.8%in the first surveillance campaign. Until October2014, after 702 observations, the average rate ofhand hygiene adherence had been 82.3%. Nonethe-less, adherence rates have been varying throughoutthe study period and are closely related to changesin the staff.

Surveillance culturesDuring the study period, between 80 and 100 weeklysamples were processed and 169 patients were colo-nized by MDR-Ab. The incidence of newly colo-nized patients decreased along with the isolation ofMDR-Ab from clinical samples, as shown in Fig. 1.From 31/12/2016 to 31/08/2017, no cases of

Fig. 1 Evolution of the incidence density rates of multidrug resistant A. baumannii: a) the whole hospital; b) the adults intensive care units

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nosocomial acquisition of MDR-Ab were detectedby surveillance cultures.

Antibiotic consumptionThe antibiotics consumption decreased during the studyperiod, as we previously reported [24]. The global antibioticconsumption in the ICU decreased from 165.35 DDD/1000to 150.44 DDD/1000 patients-days between 2012 and 2016,while the consumption of colistin reduced from 25.96 to6.65 DDD/patients-days during the same period. The con-sumption of carbepenems also decreased notably (from

31.47 to 15.9 DDD/1000 patients-days), with moderate in-crease of families with less spectrum of activity, as penicil-lins, penicillins/β-lactamase inhibitors and cephalosporins.(Evolution of the consumption of diverse antimicrobials inthe ICUs from the beginning of the whole intervention tothe end of the study is shown in Additional file 1).

DiscussionA two-decade intense endemic setting of MDR-Ab canbe eradicated. To achieve this success, we needed along-term multifaceted program, led by a

Fig. 2 PFGE profiles of ApaI-digested genomic DNA from clinical and environmental strains of A. baumannii

Table 1 Changes in rates of multidrug resistant Acinetobacter baumannii infection and colonization: results from the joinpointregression analysis

Settings Incidence Rates MDR-Ab

Pre-intervention trend Point of change 1 Post 1 trend Point of change 2 Post 2 trend

AMPC [CI95%](p-value)

Month [CI95%]p < 0.05

AMPC [CI95%](p-value)

Month [CI95%]p < 0.05

AMPC [CI95%] (p-value)

Adults hospital (ICU + wards) 0.21%[−0.40;0.82](p = 0.50)

49 [41;54](Jan/2013)

−12.14% [−17.48;-6.46](p = 0.001]

67 [53;84] (Jul/2014) 0.46 [−4.05;5.18] (p = 0.84)

ICU 0.23%[−0.25;0.71](p = 0.34)

52 [50;54](Apr/2013)

−30.05%[−55.10;8.98](p = 0.11)

56 [54;67](Aug/2013)

−2,77% [−4.91;-0.57](p = 0.01)

Adults wards 1.07% [0.01;2.13](p = 0.05)

34 [30;50](Oct/2011)

−4.02% [−5.37;-2.65](p = 0.001)

84 [61;95](Dec/2015)

3.94 [−2.40;10.70] (0.23)

AMPC Average monthly percentage change, CI confidence interval, MDR-Ab multidrug resistant Acinetobacter baumannii, ICU intensive care unit

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multidisciplinary infection-control team, and involvingthe hospital management and all the concerned staff.The efficacy of this kind of approaches is widely

supported by previous reports [25–32], with small dif-ferences among them in the measures registered,adapted to the local particularities. Many authorshave reported a complete control of MDR-Ab out-breaks in hospitals where this rod was not previously

present [28, 30–32], and many others described theefficacy of infection control programs to significantlyreduce the incidence of MDR-Ab in centres withlong-term endemic situations [25, 26, 29]. Moreover,a PDR-Ab outbreak was successfully controlled in2002–03 by a multicomponent approach in our hos-pital, but it was unable to reach a complete eradica-tion of MDR-Ab [5].

Fig. 3 Joinpoint regression analysis of the incidence density of multidrug resistant A. baumannii: a) the adult wards; b) the adult intensivecare units

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Furthermore the multifaceted approach, currentlymandatory, there were several aspects that probably en-abled these results.First of all, there is the “human factor”, that must be

considered as the essential element on the multifacetedprogram: a strong formation on antimicrobial stewardshipand infection disease management is required, with thenecessary knowledge about how to lead the intervention;the unconditional institutional support from the MedicalDirector and Director of Nurses of both the hospital andthe affected units; and also to keep the meetings with thestaff, either for education or feedback.Secondly, the relevance of keeping the actions along

the time. Despite all the efforts, we needed 6months tocontrol the endemic situation, 60 weeks to appreciate animprovement on the incidence of MDR-Ab and 94weeks to maintain these results. The persistence of res-ervoirs (colonized patients, environmental sources) andthe lack of compliance of hand hygiene or contact pre-cautions can explain this discouraging phenomenon, de-scribed in most successfully controlled MDR-Abendemic situations [25]. Thus, infection control teamsthat want to face these situations may be aware: immedi-ate effects are not expectable, and achieving successful

significant results with multifaceted programs needs along implementation period. A relevant impact willprobably appear after several months of keeping to themeasures and with periodical evaluation of possible er-rors of compliance. In addition, the occurrence of out-breaks of MDR-Ab after the eradication of the endemicsituation, caused either by community patients previ-ously colonized or patients transferred from other hospi-tals is almost warranted; which is another reason tomaintain the continuance of the program.The bundle applied was big and complex, but many of

its measures were on going previously. Why were not theyworking until the whole bundle began? Likely due to theaddition of two crucial measures: compliance assessmentand surveillance cultures with periodic feedback. Tounderstand the relevance of the first, it should bereminded that initial observations revealed that contactprecautions and hand hygiene were being poorly accom-plished. Educational meetings with those responsible forenvironmental cleaning, the development of checklistsand the direct surveillance of hand hygiene and contactprecaution accomplishment started in a context of profes-sional and institutional requirement. We opted for directobservation and checklists because of their educational

Fig. 4 Interrupted time series analysis with transition 6-month period of the incidence density of multidrug resistant A. baumannii in the intensivecare units

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effect among the several methods described to assessmentprocesses of infection control [33].The performance of surveillance cultures is part of

most programs for the control of MDR-Ab [25–27,29, 30, 32], supported by a moderate level of evidence[33]. The European Society of Clinical Microbiologyand Infectious Diseases (ESCMID) recommend activescreening cultures just for controlling the outbreaks,not for endemic situations [33]. The lack of evidenceabout the best anatomic site for culturing and a lowsensitivity of the surveillance tools to identify the car-riers have been arguments against routine screening[34]. However, a study that employed a Monte Carlomodel to assess the impact of active surveillance of A.baumannii on patient outcomes revealed that it re-duced transmissions and was cost-saving when A.baumannii prevalence was at least 2% and the screen-ing test sensitivity was 55% or higher [35]. Our ex-perience reinforces what other authors have alsoaddressed: to eradicate or significantly reduce the in-cidence in an endemic situation, screening culturesare a must.The skin is known to be a relevant reservoir of A. bau-

mannii, and skin samples are frequently included in theactive surveillance. Our program did not, and this couldconstitute a limitation of the program. There is no inter-national consensus on the samples to be taken in thesurveillance study of MDR-Ab. The guidelines of theESCMID [33] recommend: “stool samples or swab sam-ples from the rectum or perirectal area as well as sam-ples from the inguinal area and manipulated sites, e.g.catheters and areas of broken skin such as wounds”,while the HICPAC/CDC guidelines recommend takingactive screening cultures for MDR-gramnegative bacillifrom areas of skin breakdown and draining wounds and,if a respiratory tract reservoir is suspected, from endo-tracheal tube aspirates or sputum [15]. In this open sce-nario, we chose two specimens, pharyngeal and rectalswabs, because: a) respiratory colonization and infectionwas the most frequently caused by A. baumannii amongour patients; b) the sensitivity of the rectal/perianal sam-ples can achieve a 78% (higher than the sensitivity ofother localizations, as skin or wounds) [36] and the com-bination of pharyngeal and rectal sites can achieve a sen-sitivity of 96% [37]; c) several studies have related therectal colonization by MDR-Ab with a higher risk of in-fection caused by this microorganism [38, 39]. Further-more, assuming that the absence of skin screeningcultures could be a limitation of the study, it did notpreclude the goal of eradicating clinical colonization andinfection by MDR-Ab.Antimicrobial stewardship was another cornerstone

of the intervention. Although some infection controlprograms succeeded without any specific antibiotic

policy [25, 27], many others find it crucial [32, 40].As occurs with other components of the bundles, thismeasure needs to be adapted to the local scenario. Inour case, antibiotic pressure was likely the responsibleof the XDR-Ab outbreak. A careful analysis revealedthat the inappropriate duration of antimicrobial treat-ments and the overuse of carbapenems needed to beaddressed to control either the spread of A. bauman-nii or the emergence of other MDR rods.In our opinion, the main strengths in the design of this

study are the prospective data collection and the time-series analysis, which allows the most accurate analysisin non-randomized intervention studies. This kind ofanalysis, as well as previous data sustaining theemployed measures and no previous reports about thespontaneous disappearance of an endemic A. baumannii,supports the effectiveness of the presented program. Onthe other hand, another key factor on the tackling of thisendemic situation was the multifaceted program, whichreinforces our idea that a multidisciplinary and transver-sal team is necessary to achieve a more complete evalu-ation of a system of endemism, obtaining a moreeffective solution for a better care of patients. However,the study has also some limitations. Firstly, the design ofa multifaceted program prevents us from knowing if anyof the employed measures could be futile, given that allwere made simultaneously, or if adding any other meas-ure (as discussed previously for skin screening cultures)would have produced the eradication of MDR-Ab earl-ier. Secondly, although the present study reports datafrom the whole hospital, many interventions were madespecifically in the ICU; thus, the extrapolation of thesemeasures to other kind of units may require an adapta-tion. And finally, there are some issues with the suscep-tibility testing. It was not complete for all the antibioticsin all the isolates; hence, the classification as MDR/XDR/PDR relied in a number of them on the local epi-demiology and the susceptibility to the main drugs. Add-itionally, the susceptibility to colistin was performed byE-test. In 2016, few months before the study periodended, EUCAST gave “warning” for using E-test to studythe susceptibility to colistin [41], due to a risk of falsesusceptible results up to 32% [42]. We just started to useother susceptibility test methods after the study period.However, a possible misclassification of some isolates as“colistin-susceptible” would not modify the main resultsof the study.

ConclusionsThe multicomponent intervention program performedby a multidisciplinary team has been effective to con-trol the XDR-Ab outbreak and to eradicate the en-demic MDR-Ab in our hospital.

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Supplementary informationSupplementary information accompanies this paper at https://doi.org/10.1186/s13756-019-0658-4.

Additional file 1. Timeline of the measures included in the multifacetedintervention program.

AcknowledgementsWe acknowledge all the staff of the University Hospital Virgen del Rocío whoparticipated direct or indirectly in the implementation of all these measures.We also acknowledge Juan Carlos Crespo Rivas because of the revision ofthe current manuscript.

Authors’ contributionsRVM was the specialist in Preventive Medicine who worked actively in theInfection Control Team (design and implementation of the intervention,meetings) and contributed with the analysis of the data and the writing ofthe manuscript. VGG was the Microbiologist who worked in the Team andthe responsible of the surveillance cultures and the molecular typing; shealso contributed with the writing of the manuscript. RAM worked asInfectious Diseases expert in the Infection Control Team and was a majorcontributor in writing the manuscript. AMCF was the leader of the nurses inthe Infection Control Team and the responsible of the training of the staff inhand hygiene, contact precautions and environmental decontamination. TAis Intensivist and participated in the Infection Control Team, contributing tothe implementation of all the measures in the Intensive Care Unit (ICU).MVGN was the Hospital Pharmacologist of the Infection Control Team andcontributed with the implementation of the antimicrobial stewardshipprogram. IAA and CM were the chief nurses of the ICU and contributed tothe implementation of all the measures in the ICU, especially with theorganization of the training of the staff and the weekly reports. RG was theresponsible of the Cleaning Services and contributed with the organizationof the environmental cleaning and the weekly reports. EJGN and RP, asDeputy Medical Director and Deputy Chief Nurse respectively, promoted thecreation of the Infection Control Team and provided the necessary means.GP contributed with the analysis of the data. JA was the chief of theDepartment of Clinical Microbiology and provided the necessary resourcesto perform the surveillance cultures and molecular typing. MC was the chiefof the Department of Preventive Medicine and organized the necessaryhumans resources to lead all the tasks of the Infection Control Team. JMCpromoted the creation of the Infection Control Team and leaded it, activelyparticipating in all the decision, the regular meetings and especially in theantimicrobial stewardship program. All authors read and approved the finalmanuscript.

FundingThis research did not receive any specific grant from funding agencies in thepublic, commercial, or not-for-profit sectors.

Availability of data and materialsThe data that support the findings of this study are available from thearchives of the University Hospital Virgen del Rocío but restrictions apply tothe availability of these data, which were used under license for the currentstudy, and so are not publicly available. Data are however available from theauthors upon reasonable request to the corresponding author (RAM) andwith permission of the University Hospital Virgen del Rocío.

Ethics approvalLocal ethics committee declined the evaluation of this study because:a) it was not implemented as a research project, but as an institutionalprogram based in the best available evidence.b) no data from individual patients were recorded, the study just includedecological incidence data.

Consent for publicationNot applicable.

Competing interestsThe authors declare that they have no competing interests.

Author details1Departments of Infectious Diseases, Microbiology, and Preventive Medicine,University Hospital Virgen del Rocío–Institute of Biomedicine of Seville,Avenida Manuel Siurot s/n, 41013 Seville, Spain. 2Department of IntensiveCare, University Hospital Virgen del Rocío, Seville, Spain. 3Department ofPharmacy, University Hospital Virgen del Rocío, Seville, Spain. 4CleaningService, University Hospital Virgen del Rocío, Seville, Spain. 5UniversityHospital Virgen del Rocío, Seville, Spain.

Received: 3 August 2019 Accepted: 25 November 2019

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